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Biomaterials. 2011 Apr;32(10):2479-88. doi: 10.1016/j.biomaterials.2010.12.010. Epub 2010 Dec 31.

Ruthenium-catalyzed photo cross-linking of fibrin-based engineered tissue.

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  • 1Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church St., Minneapolis, MN 55455, United States.


Most cross-linking methods utilize chemistry or physical processes that are detrimental to cells and tissue development. Those that are not as harmful often do not provide a level of strength that ultimately meets the required application. The purpose of this work was to investigate the use of a ruthenium-sodium persulfate cross-linking system to form dityrosine in fibrin-based engineered tissue. By utilizing the tyrosine residues inherent to fibrin and cell-deposited proteins, at least 3-fold mechanical strength increases and 10-fold stiffness increases were achieved after cross-linking. This strengthening and stiffening effect was found to increase with culture duration prior to cross-linking such that physiologically relevant properties were obtained. Fibrin was not required for this effect as demonstrated by testing with collagen-based engineered tissue. Cross-linked tissues were implanted subcutaneously and shown to have minimal inflammation after 30 days, similar to non-cross-linked controls. Overall, the method employed is rapid, non-toxic, minimally inflammatory, and is capable of increasing strength and stiffness of engineered tissues to physiological levels.

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